To improve the efficiency of tumor diagnosis and treatment, this study developed a novel diagnostic and therapeutic nanoplatform based on gadolinium-functionalized carbon dots (Gd-CDs), providing new insights for the design of tumor therapy assisted by fluorescence/magnetic resonance imaging (FL/MRI). Gd-CDs with excellent dispersion and stable photoluminescence properties were synthesized via a one-step hydrothermal method, and hyaluronic acid (HA) was modified onto their surfaces to prepare targeting Gd-CDs (Gd-CDs-HA). Lobaplatin (LBP) was loaded on Gd-CDs-HA by electrostatic adsorption to construct the drug delivery system (Gd-CDs-HA-LBP). The average particle size of Gd-CDs-HA was 1.85 nm, with an optimal excitation wavelength of 533 nm and an optimal emission wavelength of 640 nm. The longitudinal relaxation rate r1 was 58.701 mM-1 s-1, and it exhibited a prolonged circulation time in vivo (approximately 6 h), enabling effective passive tumor targeting. When Gd-CDs-HA and LBP were mixed in a 5:2 M ratio to form Gd-CDs-HA-LBP, the maximum drug loading capacity reached 20.27%, with a release rate as high as 57.43% under acidic conditions. At a concentration of 20 μg/mL, it reduced the survival rate of H22 cells to 30.5%. It achieves efficient tumor suppression through the synergistic effect of the enhanced permeability and retention effect and active targeting in vivo, while reducing systemic toxicity (manifested as weight gain), demonstrating its high-efficiency and low-toxicity therapeutic advantages. Bioimaging experiments indicate its excellent targeting cell efficacy and FL/MRI dual-mode imaging capabilities. These results indicate that Gd-CDs-HA-LBP, as an efficient FL/MRI dual-mode imaging probe, holds great potential for application in tumor therapy.
Tumor resistance to apoptosis remains a significant obstacle in cancer therapy. In recent years, non-apoptotic cell death modalities (such as ferroptosis, pyroptosis, and lethal autophagy) have emerged as promising strategies to overcome this resistance. However, most non-apoptotic cell death inducing drugs suffer from poor targeting, low tumor enrichment efficiency, and systemic toxicity, which limit their clinical application. Metal-organic framework nanoparticles (MOF NPs), which are composed of metal ions and organic linkers, offer a compelling solution due to their tunable structures and high drug loading capacity. These features enable them to enhance therapeutic efficacy by either efficiently delivering non-apoptotic inducers or acting as direct triggers for non-apoptotic cell death. This review systematically introduces the molecular mechanisms of ferroptosis, autophagy, pyroptosis, cuproptosis, and disulfidptosis. MOF NPs have unique advantages in inducing these mechanisms. The design strategies of MOF NPs based on these mechanisms (such as material composition, surface functionalization and responsive release) are mainly summarized. The applications and efficacy of them in the targeted induction of non-apoptotic cell death are subsequently reviewed. Finally, the challenges facing this field, including biosafety, large-scale preparation, and clinical application, and future development directions are discussed and prospected.
Carbon dot (CD)-based afterglow composites have attracted significant interest for anti-counterfeiting, encryption, and bioimaging applications owing to their excellent optical properties, controllable cost, low toxicity, and environmental friendliness. However, conventional CD-based afterglow materials generally suffer from limitations including unsatisfactory structural stability, inefficient exciton utilization, and limited anti-counterfeiting potential. Therefore, there is an urgent need to develop diverse rigid matrix materials and precisely control the interactions between the matrix and CDs to achieve controlled preparation of CD-based dual-mode afterglow materials. Phenylboronic acid (PBA), with its hydroxyl and boronic acid groups, could effectively modulates CD surface states and stabilizes triplet excitons to a great extent, which is expected to serve as a promising matrix for high-performance CD-based afterglow materials. Herein, we employed a matrix-assisted strategy by embedding Cu, N-CDs with dual emission centers into a PBA matrix to construct a composite material (Cu, N-CDs@PBA) exhibiting tunable afterglow and time-evolving afterglow phenomenon during the preferred heat treatment process. The structural evolution of PBA during this heat treatment and its influence on afterglow properties were systematically investigated. The composite exhibits unique luminescence characteristics under different excitation wavelengths: blue room temperature phosphorescence (RTP) under 265 nm excitation, green RTP under 365 nm excitation, and delayed fluorescence under 450 nm excitation. These distinct emissions originate from the energy-level matching and coupling interaction between the matrix and the different emission centers of the Cu, N-CDs. Leveraging its tunable afterglow, Cu, N-CDs@PBA composite was applied as a cost-competitive and sustainable anti-counterfeiting tag for information encryption, demonstrating fascinating development prospects.
Artificial synapses have emerged as a pivotal technological advancement in mimicking brain functions. Organic memristors are desirable for hardware implementation of artificial synapses, owing to their remarkable mechanical flexibility, high biocompatibility at cell-device interfaces, and adjustable material structure. Developing appropriate organic polymers with carbon dots modification will enable the memristor to possess analog-type resistive switching behavior, crucial for realizing brain-like associative learning and adapting dynamic variations of neuron connection strength. In this work, an artificial synapse based on the analogue organic memristor integrating neuromorphic computing and neural interface functions is proposed, utilizing synthetic conjugated porous polymers to construct composites with boron-doped carbon dots. The structure-property relationship of alkynyl and alkyl chains in polymers is elucidated, alongside the synergistic effect of local photoinduced redox and hole templating in composites that endows the device with analog-type resistive switching behavior. Moreover, the memristor presents impressive synaptic plasticity and associative memory learning potential for neuromorphic computing, and further serves as a core unit in flexible artificial neural interface chips, demonstrating dynamic information transmission with neural systems. This study will promote the further development of organic artificial synapses for neuromorphic computing and brain-machine interfaces.
ABSTRACT Thermally activated delayed fluorescence (TADF) materials exhibit promising potential in the biomedical field, owing to their advantageous characteristics such as long luminescence lifetime and high fluorescence quantum yield (FLQY). However, most currently developed TADF materials have poor water solubility, which poses a significant limitation for their direct biological applications. To address this challenge and broaden their applicability in biology, the synthesis of TADF in aqueous solution has emerged as a crucial research direction in recent years. This review focuses on the latest research progress concerning TADF in aqueous solution for biomedical applications. Starting from the classification of TADF materials, it summarizes their construction strategies, performance modulation, and biomedical applications. First, based on the different methods to achieve TADF in aqueous solution, the construction strategies are categorized into three types: the matrix confinement, the self‐assembly, and the aggregation‐induced. The discussion covers the modulation of their key photophysical properties, including emission wavelength, luminescence lifetime, and FLQY. Subsequently, the review elaborates on the principles and recent advances of these materials in bioimaging, photodynamic therapy, and biosensing. Finally, the future challenges and opportunities for TADF in aqueous solution in the biomedical field are outlined, aiming to provide insights for their rational design and widespread application.
Solvent selection for electrochemical Na+-solvent co-intercalation in graphite has been constrained by an empirical rule requiring both high reductive stability and strong solvating power, thereby historically confining viable solvent candidates primarily to glyme-based ethers. Here, we re-examine this solvent selection rule and reveal that the cyclic consumption of Na+-solvent complexes at the graphite electrode and their regeneration at the counter electrode leads to a net cancellation of solvation energy in coupled electrode systems, thereby decoupling solvation power from co-intercalation feasibility. To validate this decoupling, we designed a fluorinated ether with deliberately attenuated solvating power but high reductive stability, as a proof-of-concept solvent. Successful co-intercalation was observed with this weakly solvating fluorinated ether, whereas typical carbonate solvents with superior solvation capability failed due to reductive decomposition above the intercalation threshold, confirming that solvation strength is not the determining factor. Leveraging this insight, we further designed and identified aminated ethers as a previously unexplored subclass of ethers capable of co-intercalation. This work revises the empirical dual-factor rule and eliminates solvation capability as a constraint, which broadens the range of viable solvents for graphite-based sodium-ion batteries.
Head and neck cancer is the seventh most common malignancy worldwide. Conventional treatments, including surgery, chemotherapy, radiotherapy, and immunotherapy, have achieved substantial clinical success. However, their efficacy remains limited due to treatment-associated toxicity and suboptimal therapeutic outcomes. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a promising anticancer strategy owing to its high selectivity, minimal invasiveness, and low systemic toxicity. These modalities exert antitumor effects through distinct yet complementary mechanisms. PDT utilizes a photosensitizer activated by light of a specific wavelength to generate reactive oxygen species, thereby inducing cytotoxicity. In contrast, PTT employs photothermal agents to convert light energy into heat for tumor ablation. With advances in photosensitizer design, nanotechnology, and immunotherapy, phototherapy has gained increasing attention as a potential alternative for the treatment of head and neck cancer. In this review, we provide a concise overview of the fundamental principles and mechanisms of PDT and PTT, and present recent progress in smart phototherapeutic agents. For example, liposome-based biomimetic nanodelivery systems enable precise regulation of biodistribution and release kinetics, while carbon-based materials and hybrid nanostructures have attracted considerable interest due to their multifunctionality and applicability in both PDT and PTT. Moreover, we discuss recent applications of PTT/PDT in combination with chemotherapy, immunotherapy, radiotherapy, and gene therapy for head and neck cancer. We also summarize progress regarding agents approved by the U.S. Food and Drug Administration (FDA) and ongoing clinical trials. Finally, we highlight the major challenges and future directions for the broader clinical translation of nanomedicine-based targeted phototherapy.
Cancer persists as a major global health challenge, marked by high recurrence rates in aggressive malignancies such as melanoma. While immunotherapy has emerged as a promising approach, its clinical benefits are often limited by tumor immune escape mechanisms and an immunosuppressive tumor microenvironment (TME). These hurdles have driven the exploration of integrated approaches, with photothermal-immunotherapy gaining significant traction. In this study, we developed a multifunctional nanoadjuvant (MICN@PI) engineered with an acid-responsive calcium carbonate core, a hypoxia-alleviating MnO2 component, a polydopamine shell for photothermal ablation, and co-loaded immunomodulators (imiquimod and indoximod). The MnO2 in the nanoadjuvant catalytically converted the overexpressed H2O2 in the TME into O2. Concurrently, the combined action of imiquimod and indoximod orchestrated a potent adaptive immune response. Upon near-infrared laser irradiation, MICN@PI achieved significant tumor ablation, inhibited recurrence, and prolonged survival in a murine melanoma model, offering a safe and effective synergistic photothermal-immunotherapy strategy for cancer treatment.
Narrow-bandwidth emissive carbon dots (NBE-CDs) can be well applied in light-emitting diodes (LEDs) owing to their excellent properties such as high color purity, high sensitivity, and high photoluminescence quantum yield (PLQY). Currently, most NBE-CDs achieve high PLQY fluorescence emission in solution, whereas NBE-CDs are susceptible to aggregation-caused quenching in solid state, which leads to a sharp decrease or even disappearance of fluorescence intensity. To achieve narrow-bandwidth solid-state emissive of CDs, in this work, a solution of narrow-bandwidth emissive orange CDs (O-CDs) with a full-width at half-maximum (FWHM) of 49 nm and an absolute PLQY of 83.45 % are synthesized through one-step hydrothermal method by using citric acid as carbon source and rhodamine 6G with inherent narrow FWHM as surface modifier. Subsequently, the O-CDs are dispersed in a polyvinylpyrrolidone (PVP) matrix to form O-CDs/PVP fluorescent films, which retains a narrow FWHM of 49 nm and exhibits a PLQY of 59.4 %, thereby enabling solid-state emission. Combining experimental and theoretical simulations, it is found that the solvent environment plays a critical role in determining the FWHM of O-CDs. Specifically, the FWHM gradually decreases as the proton donating capacity gradually weakens and the degree of dispersion deepens. Finally, high-color-purity photoluminescent LEDs with an FWHM of 49 nm are fabricated by combining the O-CDs/PVP fluorescent films with blue LEDs chips. This work provides both theoretical and experimental foundations for the controllable synthesis of efficient narrow-bandwidth solid-state emissive CDs.
The detection of procalcitonin (PCT) levels is of great significance for the early diagnosis of bacterial infections and the evaluation of therapeutic efficacy. As a highly specific and sensitive biomarker, PCT not only effectively distinguishes bacterial from viral infections but also reflects real-time changes in disease progression, providing critical support for precision clinical diagnosis and treatment. In this study, a transition metal-based layered double hydroxide (Cu-FeNi LDH) with high specific surface area was employed as a substrate and decorated with highly conductive gold nanoparticles (AuNPs) to fabricate a hybrid electrode sensing material (AuNPs@Cu-FeNi LDH) that integrates the advantages of both components. This material was subsequently used to construct an electrochemical immunosensor for highly efficient PCT detection. The nano-hydrangea-like structure of AuNPs@Cu-FeNi LDH significantly increases the composite surface area, providing abundant active sites for redox reactions. The attachment of AuNPs between the hydrangea petals facilitates surface functionalization, enabling specific binding with PCT antibodies and thereby enhancing sensor selectivity. Experimental results demonstrate that the proposed sensor exhibits a wide linear range, low detection limit, as well as good selectivity, reproducibility, and stability for PCT detection. Recovery experiments using spiked human serum samples further validated the accuracy of the sensor for real sample analysis. This study provides a feasible strategy for the application of electrochemical immunosensors in the clinical detection of PCT.
Early diagnosis and precise treatment of liver cancer represent critical directions in medical research. Theranostic strategies integrating bioimaging and drug delivery have demonstrated significant potential, offering advantages such as high precision, enhanced imaging clarity, and improved therapeutic efficacy. Room temperature phosphorescence carbon dots@silica composites (RTP CDs@SiO2) stand out in bioimaging for their excellent properties such as long phosphorescence lifetime and low toxicity. However, their irregular morphology and large particle size restrict applications in drug delivery. In this study, RTP CDs@SiO2 composites were synthesized in an an aqueous solution via three approaches with different alkaline additives: no alkaline additive, ammonia solution, and arginine. Through the synergistic effect of the guanidine group, amino group, and carboxyl group in arginine molecules, nanoparticles with an average particle size of 14.2 nm, a phosphorescence lifetime of 1398.91 ms, and a visible afterglow duration of 12 s were prepared. The resultant composites possessed favorable biocompatibility with low toxicity, as well as outstanding phosphorescence imaging performance both in vitro and in vivo. The RTP CDs drug delivery system (CDs@SiO2-HA-DOX) was further constructed by loading the targeting molecule hyaluronic acid (HA) and the chemotherapy drug doxorubicin (DOX) via electrostatic adsorption and covalent coupling using CDs@SiO2 as a carrier. Results demonstrated that this system achieved a maximum drug loading capacity of 49.39% and exhibited pH-dependent DOX release under weakly acidic conditions. In vitro antitumor experiments revealed that CDs@SiO2-HA-DOX reduced the viability of HepG2 cells to 22.95%. In vivo studies using tumor-bearing mouse models confirmed a tumor inhibition rate of 75.48%, demonstrating significant antitumor efficacy. This work represents the first successful application of RTP CD composites in drug delivery. The developed system shows great promise as a theranostic candidate for liver cancer by integrating drug delivery and RTP imaging, highlighting its significant potential for cancer therapy applications.
Hepatocellular carcinoma (HCC), a predominant subtype of liver cancer, is witnessing a rising global incidence and urgently demands the development of innovative nanoplatforms that integrate precise therapeutic and immune regulatory functions. To address the limitations of conventional monotherapies, which often suffer from inadequate tumor targeting, insufficient efficacy, and limited immune activation, this study employs a "biomimetic targeting-synergy therapy" approach. We have engineered a composite system consisting of gadolinium-doped carbon dots (Gd-CDs) enveloped with hepatocellular carcinoma cell membranes (HCM), thereby imparting homologous targeting capabilities and immune activation properties. This Gd-CDs@HCM system facilitates photothermal immunotherapy, guided by bimodal fluorescence (FL) and magnetic resonance (MR) imaging. Upon laser irradiation, Gd-CDs@HCM can induce immunogenic cell death (ICD) in tumor cells. The tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) released during ICD collaboratively enhance systemic anti-tumor immunity in conjunction with HCM, achieving a primary tumor ablation rate of 84.9% and inhibiting tumor progression. Consequently, this research offers an innovative strategy for real-time monitoring and precise synergistic treatment of HCC by utilizing FL/MR bimodal imaging and integrating bionic targeting, localized thermal ablation, and immune activation functions.
Gouty arthritis (GA), caused by monosodium urate crystal deposition in the context of persistent hyperuricemia, remains difficult to treat due to the inability of conventional therapies to simultaneously control uric acid (UA) levels, oxidative stress, and inflammation. To overcome this, we develop a biomimetic nanozyme composed of AuPt bimetallic nanozymes cloaked with erythrocyte membrane (AuPt@EM). It integrates prolonged circulation with cascade enzyme activities to achieve systemic UA reduction, local crystal clearance, and modulation of the inflammatory hypoxic microenvironment. AuPt@EM exhibits superoxide dismutase-like and catalase-like activities, efficiently scavenging ROS and generating oxygen, thereby amplifying its uricase-like activity to sustainably reduce UA. This nanozyme reduces ROS, suppresses the PI3K/AKT/HIF-1 alpha pathway, and promotes HIF-1 alpha degradation, which reprograms macrophages from the pro-inflammatory M1 phenotype toward the antiinflammatory M2 phenotype. In vivo, AuPt@EM facilitates crystal clearance, alleviates joint inflammation, and preserves cartilage integrity. Moreover, it restores systemic immune balance by elevating IL-10 while decreasing IL-1(3 and IL-6. This study establishes an integrated therapeutic paradigm that combines UA level control, crystal dissolution, and inflammatory hypoxic microenvironment modulation, offering a promising strategy for precise and effective intervention in hyperuricemia and gouty arthritis.
Neural interfaces demand memristor-based artificial synapses with comprehensive performance for neuromorphic computing and man-machine interaction. This study proposes a halogen doping engineering to enhance carbon dots (CDs)-based memristors performance for artificial synapses. Halogen-doped CDs (FCDs, ClCDs, BrCDs) and undoped CDs (UCDs) were synthesized via a solvothermal method. Systematic characterization confirms successful doping and reveals that Br doping optimally modulates electronic structure. The BrCDs-based memristor demonstrates the best memristor performance among these devices. Experimental and computational results illustrate that appropriate electronegativity of Br atoms can facilitate electron trapping and detrapping process. As a bioinspired synapse, the device successfully mimics key short-term and long-term plasticity, and demonstrates excellent performance in image classification tasks. Furthermore, the BrCDs-based device serves as the core of an artificial neural interface chip, successfully enabling chemical neurotransmitter dopamine release and eliciting Ca2+ responses in PC12 cells, realizing information communication with the neural system and addressing the mismatch between conventional electronic interfaces and the chemical signaling of biological synapses. This work exhibits the potential of halogen-doped CDs, particularly BrCDs, in advancing artificial synapses integrating the functions of neuromorphic computing and adaptive learning interaction.
The widespread use of silicone rubber medical devices is hindered by their susceptibility to surface infections, a serious clinical challenge. Although silver nanoparticles (AgNPs) exhibit high antibacterial efficacy, their biomedical application is limited by aggregation, oxidation, uncontrolled Ag+ release, and potential toxicity risks. To address these limitations, this study proposes a simple and efficient modification strategy based on carbon-coated silver nanoparticles (Ag@C). Ag@C particles were synthesized via a one-step hydrothermal method, and long-lasting antibacterial silicone rubber (Ag@C-SR) was successfully constructed through a straightforward blending and vulcanization process. The results demonstrated that Ag@C achieved an antibacterial rate of up to 99% against both E. coli and S. aureus, while maintaining favorable biocompatibility. Mechanistic investigations revealed that the antibacterial activity of Ag@C was mainly attributed to the synergistic effects of sustained Ag+ release, ROS-mediated oxidative damage, and the functional contribution of the carbon layer. An optimal Ag@C loading of 0.9 wt% was determined, under which Ag@C-SR exhibited sustained Ag+ release for 28 days and achieved 62.0% inhibition of biofilm formation. In vivo rat experiments further showed that Ag@C-SR reduced the bacterial load at the infection site by approximately two orders of magnitude without inducing significant inflammation. Overall, this study provides a feasible strategy for overcoming the limitations of conventional AgNPs-based antibacterial agents and establishes a material foundation for developing silicone rubber medical devices with long-term anti-infective function and potential clinical applicability.
Gadolinium functionalized carbon dot complexes (Gd-CDs) have both the fluorescent properties of carbon dots and the magnetic characteristics of gadolinium ions, exhibiting excellent biocompatibility, high spatial resolution, high sensitivity, and deep tissue penetration in bioimaging. As fluorescence (FL) and magnetic resonance imaging (MRI) probes, Gd-CDs have attracted significant attention in dual-modal biological imaging. This review summarizes recent advances in Gd-CDs, focusing on their structure, optical and magnetic properties, and applications in dual-modal imaging. First, according to the different existing forms of gadolinium in carbon dots, the structures of Gd-CDs are categorized into chelation, electrostatic interaction, and encapsulation. Second, the mechanisms and performances of Gd-CDs in dual-modal imaging are introduced in detail. The reported Gd-CDs have a maximum quantum yield of 69.86%, with a fluorescence emission wavelength reaching up to 625 nm, and the optimum longitudinal and transverse relaxivity rates are 35.39 and 115.6 mM-1 s-1, respectively, showing excellent FL/MRI capacities. Subsequently, the progress in their applications in dual-modal cellular imaging, in vivo imaging, and integrated cancer diagnosis and therapy is reviewed. Finally, the challenges and issues faced by Gd-CDs in their development are summarized, providing new insights for their controlled synthesis and widespread application in the biomedical field of dual-modal imaging.
A simple and rapid one-step microwave-assisted method was employed to synthesize solid-state red emissive carbon dots (R-CDs) using phloroglucinol, urea, and ammonium fluoride in a high-boiling point solvent. Raw material ratios and solvent types were investigated. The optimal emission of R-CDs at 625 nm was achieved when the molar ratio was 3:1:6 in a 50% N, N-dimethyl formamide/water for 15 min. When formamide and water (v/v = 5:95) were used, R-CDs with longer emission (640 nm) were obtained and the reaction time was shortened to 3 min, enhancing both efficiency and cost-effectiveness. Both R-CDs maintained >96% fluorescence intensity after UV exposure and <5% weight loss at 200°C. Combined with polyvinyl pyrrolidone, R-CDs baesed red LEDs with CIE coordinates (0.67, 0.33) and (0.62, 0.38) were achieved. Combined with blue/green CDs, white LEDs showed color rendering indexes of 91-92. This study advances solid-state red CDs for high-quality white LEDs.